Five to 10 percent of patients entering general practice centers report symptoms of fibromyalgia syndrome (FMS), a painful and debilitating condition of the musculoskeletal system. Although the cause(s) and pathophysiology of this disorder are poorly understood, FMS has been referred to as a syndrome of physical deconditioning and involves dysregulation of the hypothalamic- pituitary-adrenal (HPA) axis. Interestingly, regular exercise has been shown to confer benefit for some patients with FMS, as well as rheumatoid arthritis and depression. Importantly these health conditions all have the common element of reduced hypothalamic drive for pituitary adrenal function. Thus, exercise may confer benefit in FMS by upregulating hypothalamic drive to the pituitary and adrenal glands. The overall objective of this proposal is to determine whether aerobic training benefits FMS by inducing alternations in HPA axis regulation. The central hypothesis is that aerobic training serves to enhance hypothalamic drive, and thus pituitary-adrenal function. Specifically, 20 patients with FMS and 20 age-, gender-, weight-matched controls will be challenged at baseline; after 12 weeks with no intervention (control), and after 12 weeks of aerobic conditioning to evaluate whether aerobic training results in: (1) An increase in hypothalamic drive as evidenced by augmented adrenocorticotropin (ACTH) responses to a standardized exercise test (SET); (2) An increase in tonic and stimulated hypothalamic drive as evidenced by augmented ACTH responses following administration of metyrapone and dexamethasone (DEX) coupled with SET; (3) An increase in hypothalamic-pituitary responsiveness as evidenced by augmented ACTH responses stimulated by a bolus of ovine corticotropin releasing hormone (o-CRH) after pretreatment with DEX; and (4) Improved clinical and psychological profiles in FMS. Plasma ACTH will be used to assess hypothalamic drive during four challenge tests: (a) SET for control stimulation; (b) SET during enhancement of glucocorticoid negative feedback by DEX; (c) tonic and SET during attenuation of glucocorticoid negative feedback by metyrapone; and (d) responsivity of pituitary corticotropes following a bolus of o-CRH during enhancement of glucocorticoid negative feedback by DEX. Finally, disease activity (tender point index, tender point score, and myalgic score), and self-reported physical measures of function, depression and self efficacy will be used to assess clinical and psychological profiles over the course of the study. The information gained will provide an understanding of the pathology of FMS and the mechanisms by which exercise confers benefit in FMS. Given the important role exercise serves in the prevention of disease, this information will also contribute to our basic knowledge regarding how exercise modulates HPA axis reactivity in health and, in so doing suggest, mechanisms for HPA dysregulation in disease.